Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1993 Aug 1;293(Pt 3):649–655. doi: 10.1042/bj2930649

Correlation between secretion and phospholipase D activation in differentiated HL60 cells.

J Stutchfield 1, S Cockcroft 1
PMCID: PMC1134415  PMID: 8352731

Abstract

Receptor-directed agonists including N-formylmethionyl-leucyl-phenylalanine (fMetLeuPhe), C5a, ATP and UTP all activate phospholipase D (PLD), which is accompanied by secretion in differentiated HL60 cells. Interference in the production of phosphatidase (PA) by the PLD pathway by diverting it towards the production of phosphatidylethanol (PEt) in the presence of ethanol leads to near-total inhibition of the secretion evoked by ATP and UTP and a partial inhibition of that evoked by fMetLeuPhe and C5a. In streptolysin-O-permeabilized cells, fMetLeuPhe is able to activate PLD, and this is dependent on the presence of a low concentration of guanosine 5'-[gamma-thio]-triphosphate (GTP[S]). Ca2+ (10 microM) and GTP[S] individually or in combination are also able to activate PLD and secretion. The stimulation of secretion in permeabilized cells stimulated by Ca2+ alone or fMetLeuPhe or GTP[S] is also abrogated when the production of PA is diverted to PEt by the presence of ethanol. Activation of PLD by GTP[S] or fMetLeuPhe is decreased if the cells are permeabilized first and GTP[S] or fMetLeuPhe is added subsequently. This corresponds well with the loss of the secretory response. We conclude that the ability of GTP[S] or fMetLeuPhe to stimulate secretion from permeabilized cells is dependent on a prior activation of the PLD signalling pathway. PA, generated as a consequence of PLD activation, acts as second messenger that can provide an initiating signal for secretion and is not required for exocytosis itself.

Full text

PDF
649

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abo A., Pick E., Hall A., Totty N., Teahan C. G., Segal A. W. Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1. Nature. 1991 Oct 17;353(6345):668–670. doi: 10.1038/353668a0. [DOI] [PubMed] [Google Scholar]
  2. Agwu D. E., McPhail L. C., Sozzani S., Bass D. A., McCall C. E. Phosphatidic acid as a second messenger in human polymorphonuclear leukocytes. Effects on activation of NADPH oxidase. J Clin Invest. 1991 Aug;88(2):531–539. doi: 10.1172/JCI115336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anthes J. C., Wang P., Siegel M. I., Egan R. W., Billah M. M. Granulocyte phospholipase D is activated by a guanine nucleotide dependent protein factor. Biochem Biophys Res Commun. 1991 Feb 28;175(1):236–243. doi: 10.1016/s0006-291x(05)81225-2. [DOI] [PubMed] [Google Scholar]
  4. Barrowman M. M., Cockcroft S., Gomperts B. D. Differential control of azurophilic and specific granule exocytosis in Sendai-virus-permeabilized rabbit neutrophils. J Physiol. 1987 Feb;383:115–124. doi: 10.1113/jphysiol.1987.sp016399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barrowman M. M., Cockcroft S., Gomperts B. D. Two roles for guanine nucleotides in the stimulus-secretion sequence of neutrophils. Nature. 1986 Feb 6;319(6053):504–507. doi: 10.1038/319504a0. [DOI] [PubMed] [Google Scholar]
  6. Billah M. M., Eckel S., Mullmann T. J., Egan R. W., Siegel M. I. Phosphatidylcholine hydrolysis by phospholipase D determines phosphatidate and diglyceride levels in chemotactic peptide-stimulated human neutrophils. Involvement of phosphatidate phosphohydrolase in signal transduction. J Biol Chem. 1989 Oct 15;264(29):17069–17077. [PubMed] [Google Scholar]
  7. Bocckino S. B., Wilson P. B., Exton J. H. Phosphatidate-dependent protein phosphorylation. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6210–6213. doi: 10.1073/pnas.88.14.6210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bonser R. W., Thompson N. T., Randall R. W., Garland L. G. Phospholipase D activation is functionally linked to superoxide generation in the human neutrophil. Biochem J. 1989 Dec 1;264(2):617–620. doi: 10.1042/bj2640617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Churcher Y., Allan D., Gomperts B. D. Relationship between arachidonate generation and exocytosis in permeabilized mast cells. Biochem J. 1990 Feb 15;266(1):157–163. doi: 10.1042/bj2660157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cockcroft S., Allan D. The fatty acid composition of phosphatidylinositol, phosphatidate and 1,2-diacylglycerol in stimulated human neutrophils. Biochem J. 1984 Sep 1;222(2):557–559. doi: 10.1042/bj2220557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cockcroft S. Ca2+-dependent conversion of phosphatidylinositol to phosphatidate in neutrophils stimulated with fMet-Leu-Phe or ionophore A23187. Biochim Biophys Acta. 1984 Aug 15;795(1):37–46. doi: 10.1016/0005-2760(84)90102-4. [DOI] [PubMed] [Google Scholar]
  12. Cockcroft S. G-protein-regulated phospholipases C, D and A2-mediated signalling in neutrophils. Biochim Biophys Acta. 1992 Aug 14;1113(2):135–160. [PubMed] [Google Scholar]
  13. Cockcroft S., Howell T. W., Gomperts B. D. Two G-proteins act in series to control stimulus-secretion coupling in mast cells: use of neomycin to distinguish between G-proteins controlling polyphosphoinositide phosphodiesterase and exocytosis. J Cell Biol. 1987 Dec;105(6 Pt 1):2745–2750. doi: 10.1083/jcb.105.6.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Cockcroft S. Relationship between arachidonate release and exocytosis in permeabilized human neutrophils stimulated with formylmethionyl-leucyl-phenylalanine (fMetLeuPhe), guanosine 5'-[gamma-thio]triphosphate (GTP[S]) and Ca2+. Biochem J. 1991 Apr 1;275(Pt 1):127–131. doi: 10.1042/bj2750127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cockcroft S., Thomas G. M. Inositol-lipid-specific phospholipase C isoenzymes and their differential regulation by receptors. Biochem J. 1992 Nov 15;288(Pt 1):1–14. doi: 10.1042/bj2880001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cromwell O., Bennett J. P., Hide I., Kay A. B., Gomperts B. D. Mechanisms of granule enzyme secretion from permeabilized guinea pig eosinophils. Dependence on Ca2+ and guanine nucleotides. J Immunol. 1991 Sep 15;147(6):1905–1911. [PubMed] [Google Scholar]
  17. Geny B., Cockcroft S. Synergistic activation of phospholipase D by protein kinase C- and G-protein-mediated pathways in streptolysin O-permeabilized HL60 cells. Biochem J. 1992 Jun 1;284(Pt 2):531–538. doi: 10.1042/bj2840531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Geny B., Stutchfield J., Cockcroft S. Phorbol ester inhibits polyphosphoinositide phosphodiesterase activity stimulated by either Ca2+, fluoride or GTP analogue in HL60 membranes and in permeabilized HL60 cells. Cell Signal. 1989;1(2):165–172. doi: 10.1016/0898-6568(89)90006-5. [DOI] [PubMed] [Google Scholar]
  19. Gomperts B. D. GE: a GTP-binding protein mediating exocytosis. Annu Rev Physiol. 1990;52:591–606. doi: 10.1146/annurev.ph.52.030190.003111. [DOI] [PubMed] [Google Scholar]
  20. Goud B., Salminen A., Walworth N. C., Novick P. J. A GTP-binding protein required for secretion rapidly associates with secretory vesicles and the plasma membrane in yeast. Cell. 1988 Jun 3;53(5):753–768. doi: 10.1016/0092-8674(88)90093-1. [DOI] [PubMed] [Google Scholar]
  21. Kanaho Y., Kanoh H., Saitoh K., Nozawa Y. Phospholipase D activation by platelet-activating factor, leukotriene B4, and formyl-methionyl-leucyl-phenylalanine in rabbit neutrophils. Phospholipase D activation is involved in enzyme release. J Immunol. 1991 May 15;146(10):3536–3541. [PubMed] [Google Scholar]
  22. Knaus U. G., Heyworth P. G., Evans T., Curnutte J. T., Bokoch G. M. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science. 1991 Dec 6;254(5037):1512–1515. doi: 10.1126/science.1660188. [DOI] [PubMed] [Google Scholar]
  23. Lillie T. H., Gomperts B. D. Nucleotides and divalent cations as effectors and modulators of exocytosis in permeabilized rat mast cells. Philos Trans R Soc Lond B Biol Sci. 1992 Apr 29;336(1276):25–34. doi: 10.1098/rstb.1992.0040. [DOI] [PubMed] [Google Scholar]
  24. Morgan A., Burgoyne R. D. Stimulation of Ca2(+)-independent catecholamine secretion from digitonin-permeabilized bovine adrenal chromaffin cells by guanine nucleotide analogues. Relationship to arachidonate release. Biochem J. 1990 Jul 15;269(2):521–526. doi: 10.1042/bj2690521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mullmann T. J., Siegel M. I., Egan R. W., Billah M. M. Complement C5a activation of phospholipase D in human neutrophils. A major route to the production of phosphatidates and diglycerides. J Immunol. 1990 Mar 1;144(5):1901–1908. [PubMed] [Google Scholar]
  26. Oberhauser A. F., Monck J. R., Balch W. E., Fernandez J. M. Exocytotic fusion is activated by Rab3a peptides. Nature. 1992 Nov 19;360(6401):270–273. doi: 10.1038/360270a0. [DOI] [PubMed] [Google Scholar]
  27. Olson S. C., Bowman E. P., Lambeth J. D. Phospholipase D activation in a cell-free system from human neutrophils by phorbol 12-myristate 13-acetate and guanosine 5'-O-(3-thiotriphosphate). Activation is calcium dependent and requires protein factors in both the plasma membrane and cytosol. J Biol Chem. 1991 Sep 15;266(26):17236–17242. [PubMed] [Google Scholar]
  28. Padfield P. J., Balch W. E., Jamieson J. D. A synthetic peptide of the rab3a effector domain stimulates amylase release from permeabilized pancreatic acini. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1656–1660. doi: 10.1073/pnas.89.5.1656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pai J. K., Siegel M. I., Egan R. W., Billah M. M. Activation of phospholipase D by chemotactic peptide in HL-60 granulocytes. Biochem Biophys Res Commun. 1988 Jan 15;150(1):355–364. doi: 10.1016/0006-291x(88)90528-1. [DOI] [PubMed] [Google Scholar]
  30. Preiss J. E., Bell R. M., Niedel J. E. Diacylglycerol mass measurements in stimulated HL-60 phagocytes. J Immunol. 1987 Mar 1;138(5):1542–1545. [PubMed] [Google Scholar]
  31. Rhee S. G., Choi K. D. Regulation of inositol phospholipid-specific phospholipase C isozymes. J Biol Chem. 1992 Jun 25;267(18):12393–12396. [PubMed] [Google Scholar]
  32. Rossi F., Grzeskowiak M., Della Bianca V., Calzetti F., Gandini G. Phosphatidic acid and not diacylglycerol generated by phospholipase D is functionally linked to the activation of the NADPH oxidase by FMLP in human neutrophils. Biochem Biophys Res Commun. 1990 Apr 16;168(1):320–327. doi: 10.1016/0006-291x(90)91711-z. [DOI] [PubMed] [Google Scholar]
  33. Salminen A., Novick P. J. A ras-like protein is required for a post-Golgi event in yeast secretion. Cell. 1987 May 22;49(4):527–538. doi: 10.1016/0092-8674(87)90455-7. [DOI] [PubMed] [Google Scholar]
  34. Segev N., Mulholland J., Botstein D. The yeast GTP-binding YPT1 protein and a mammalian counterpart are associated with the secretion machinery. Cell. 1988 Mar 25;52(6):915–924. doi: 10.1016/0092-8674(88)90433-3. [DOI] [PubMed] [Google Scholar]
  35. Senyshyn J., Balch W. E., Holz R. W. Synthetic peptides of the effector-binding domain of rab enhance secretion from digitonin-permeabilized chromaffin cells. FEBS Lett. 1992 Aug 31;309(1):41–46. doi: 10.1016/0014-5793(92)80735-y. [DOI] [PubMed] [Google Scholar]
  36. Smolen J. E., Stoehr S. J., Boxer L. A. Human neutrophils permeabilized with digitonin respond with lysosomal enzyme release when exposed to micromolar levels of free calcium. Biochim Biophys Acta. 1986 Apr 8;886(1):1–17. doi: 10.1016/0167-4889(86)90205-3. [DOI] [PubMed] [Google Scholar]
  37. Smolen J. E., Stoehr S. J. Guanine nucleotides reduce the free calcium requirement for secretion of granule constituents from permeabilized human neutrophils. Biochim Biophys Acta. 1986 Nov 28;889(2):171–178. doi: 10.1016/0167-4889(86)90101-1. [DOI] [PubMed] [Google Scholar]
  38. Smolen J. E., Stoehr S. J., Traynor A. E., Sklar L. A. The kinetics of secretion from permeabilized human neutrophils: release of elastase and correlations with other granule constituents and right angle light scatter. J Leukoc Biol. 1987 Jan;41(1):8–13. doi: 10.1002/jlb.41.1.8. [DOI] [PubMed] [Google Scholar]
  39. Stutchfield J., Cockcroft S. Characterization of fMet-Leu-Phe-stimulated phospholipase C in streptolysin-O-permeabilised cells. Eur J Biochem. 1991 Apr 10;197(1):119–125. doi: 10.1111/j.1432-1033.1991.tb15889.x. [DOI] [PubMed] [Google Scholar]
  40. Stutchfield J., Cockcroft S. Guanine nucleotides stimulate polyphosphoinositide phosphodiesterase and exocytotic secretion from HL60 cells permeabilized with streptolysin O. Biochem J. 1988 Mar 1;250(2):375–382. doi: 10.1042/bj2500375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tettenborn C. S., Mueller G. C. 12-O-tetradecanoylphorbol-13-acetate activates phosphatidylethanol and phosphatidylglycerol synthesis by phospholipase D in cell lysates. Biochem Biophys Res Commun. 1988 Aug 30;155(1):249–255. doi: 10.1016/s0006-291x(88)81076-3. [DOI] [PubMed] [Google Scholar]
  42. Uings I. J., Thompson N. T., Randall R. W., Spacey G. D., Bonser R. W., Hudson A. T., Garland L. G. Tyrosine phosphorylation is involved in receptor coupling to phospholipase D but not phospholipase C in the human neutrophil. Biochem J. 1992 Feb 1;281(Pt 3):597–600. doi: 10.1042/bj2810597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wheeler-Jones C. P., Saermark T., Kakkar V. V., Authi K. S. Mastoparan promotes exocytosis and increases intracellular cyclic AMP in human platelets. Evidence for the existence of a Ge-like mechanism of secretion. Biochem J. 1992 Jan 15;281(Pt 2):465–472. doi: 10.1042/bj2810465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Xie M. S., Dubyak G. R. Guanine-nucleotide- and adenine-nucleotide-dependent regulation of phospholipase D in electropermeabilized HL-60 granulocytes. Biochem J. 1991 Aug 15;278(Pt 1):81–89. doi: 10.1042/bj2780081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Xie M. S., Jacobs L. S., Dubyak G. R. Regulation of phospholipase D and primary granule secretion by P2-purinergic- and chemotactic peptide-receptor agonists is induced during granulocytic differentiation of HL-60 cells. J Clin Invest. 1991 Jul;88(1):45–54. doi: 10.1172/JCI115303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Yuli I., Tomonaga A., Synderman R. Chemoattractant receptor functions in human polymorphonuclear leukocytes are divergently altered by membrane fluidizers. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5906–5910. doi: 10.1073/pnas.79.19.5906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Zahraoui A., Touchot N., Chardin P., Tavitian A. The human Rab genes encode a family of GTP-binding proteins related to yeast YPT1 and SEC4 products involved in secretion. J Biol Chem. 1989 Jul 25;264(21):12394–12401. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES